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In addition, copper is also involved in the binding of HIF-1α to the hypoxia response element (HRE) sequence of target genes, which requires the copper molecular chaperone CCS, and activates EMT-related genes such as snail family transcriptional repressor 1 (SNAIL1), twist-related protein 1 (TWIST1), snail family transcriptional repressor 2 (SNAIL2), zinc finger E-box-binding homeobox 1 (ZEB1), zinc finger E-box-binding homeobox 2 (ZEB2), and E12/E47 ( Therefore, copper can affect the activity of LOX and LOXL enzymes, the expression of MEMO1, and the binding of HIF-1α to target genes with HRE sequences (hypoxia response elements), thereby regulating the expression of EMT-related genes and promoting tumor cell metastasis

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